July 9, 2018
Using surface-enhanced Raman spectroscopy (SERS) to uncover the mysteries of circulating tumor DNA in the bloodstream, an innovative Ph.D. candidate from Johns Hopkins University encourages others to bravely tackle research problems outside their areas of expertise. “You can apply what you know already to answer questions in life sciences.”
After reviewing 21 proposals from candidates at 19 different institutions, SLAS named Santosh Paidi recipient of the 2018 SLAS Graduate Education Fellowship Grant. Paidi, a graduate research assistant in the Department of Mechanical Engineering at Johns Hopkins University (Baltimore, MD), will use the $100,000 grant, to be awarded over two years, to continue his work in the lab of Ishan Barman, Ph.D., where the team develops diagnostic tools to provide rapid, robust, quantitative and molecular-specific readouts from biological specimens.
Paidi’s research utilizes a sensitive, multiplexed, rapid diagnostic assay that can measure metastatic disease with high sensitivity and specificity and monitor subtle changes in tumor burden to aid in decision analysis for optimal treatment strategies. His research also includes creating an integrated platform for cell capture and multiplexed, non-perturbative measurement of the cell surface molecular expression to construct maps of cell surface protein glycation, which remains a poorly understood process despite its significance in tumor formation and metastasis.
“This assay combines several diverse areas of expertise – optics, biology, medicine, engineering and machine learning – that address and develop solutions that touch human life,” Paidi says.
Spurred by recent implementation of SERS assays for protein biomarkers detection in sera and development of single cell analysis platforms for live cell imaging, Paidi envisions that his current project will open new photonic routes for quantification of circulating cancer biomarkers as well as for high-definition visualization of cell-surface glycosylation. The goal is to develop new diagnostic tools for unmet needs in breast cancer diagnosis, prognosis, therapeutic response or resistance monitoring. Paidi hopes to generate strong proof-of-concept data on which the lab can pursue exploratory clinical studies to test the assay’s efficacy in detecting metastatic disease in suitable patient cohorts.
“Raman spectroscopy allows us to dig into a biological question without needing to know as much about a specific disease or having a particular target,” Paidi says. “Using label-free approaches allows us to study the disease in an unbiased way.”
Barman comments that Paidi’s research is a good fit with SLAS’s mission to further life sciences discovery and technology. “I think this work will reveal fundamental insights into the cellular behavior of pathological mechanisms,” says Barman. “The research also will allow us to develop tools that can be clinically translated in point-of-care settings, which is particularly important in under-resourced facilities where there is a paucity of significant resources, manpower or scientific expertise. These are fresh ideas in an increasingly competitive arena.”
Barman calls spectroscopic imaging an extremely powerful tool for disease diagnostics. “It combines the molecular basis of spectroscopy with the imaging capabilities of microscopy, presenting what we consider to be a natural bridge between the chemical and the morphologic domains,” he continues. “When paired with certain kinds of nanostructured plasmonic probes, spectroscopic imaging allows Santosh to use SERS to discover more about human antigens such as circulating tumor markers, tumor antigens and hypermethylated DNA.” Spectroscopic imaging also allows Paidi to pursue single-cell analysis, which is the second major project he is developing – formulating or monitoring cells without perturbing them in any significant way.
Describing Paidi as an exceptional student researcher, Barman adds “there's a transition process in graduate school in which a student becomes an independent researcher who can be a principal investigator leading his own program in the future. The SLAS Graduate Education Fellowship Grant’s structure helps students to become independent thinkers and allows students to pursue highly innovative and creative work that has a high pay-off,” Barman says.
Paidi agrees. He feels that he has earned the grant at just the right time in his studies. “The next two years are crucial for me to summarize my existing work and launch new projects that I can advance as an independent researcher,” he explains. He adds that the grant will allow him to do more research in areas that have not been as actively explored because of a lack of certain resources. “This grant opens doors to challenging questions, one of which is how to quantitatively access the DNA of circulating tumor cells.”
Paidi reports that his research experiences up to this point taught him to value each step of his education. “Current engineering curriculums – both here and in India – prepare you to tackle many different problems,” says Paidi, who has a bachelor’s degree in mechanical engineering, with a minor in aerospace engineering from the Indian Institute of Technology (IIT), Bombay. “My diverse lab experiences have shown me that it doesn’t matter what field your research and expertise are in, as long as you make an effort to understand problems and develop solutions.”
During summer breaks during his undergraduate studies, Paidi worked first in a lab with microfluidics, then in a lab studying hydrogen combustion. “When I joined the lab studying microfluidics, the PI was open about choosing projects. He wanted me to see what everyone was doing and then select research that I wanted to continue,” says Paidi. “I worked in the lab for more than a year and gained some exposure to microfabrication and creating microfluidic chips and studying flows in those chips.”
The following summer, he explored using hydrogen as a fuel. “Our team experimented with different dilutions using carbon dioxide and nitrogen to study their impact on flame velocity and performance of hydrogen-air mixtures. I worked on it for a couple of years, published an article and presented my published research at a conference. It was important exposure for my research and degree program,” says Paidi, whose efforts resulted in nine peer-reviewed publications.
During this time, Paidi also conducted research on electrowetting, observing how droplets of water or another liquid change and spread on certain kinds of substrates when electric voltage is applied. “My goal was to design and improve the substrate being used in the research,” he explains. “What I wanted to achieve was more wetting with less voltage.”
During this project, Paidi collaborated with a scientist based in the Massachusetts Institute of Technology (MIT)’s Lincoln Laboratory. “We started the project when he was a visiting faculty at IIT Bombay for a year. After he left, I continued working on it under his remote guidance,” says Paidi, adding that the project showed him how collaboration among researchers with diverse expertise contributes to research progress.
“Knowing that my expertise can contribute to scientific problems has helped me jump into biophotonics, an area that I had barely heard of before I applied to graduate school,” Paidi says. As he began his search for a graduate school, Paidi noticed that many universities, particularly in the United States, have a strong bio-focus in their mechanical engineering departments. The program at Johns Hopkins was no different, and when he examined the institution’s graduate program as an option, the background of faculty member Ishan Barman stood out to him.
“As I looked at his research and published papers, I saw that he also had a background very similar to mine, as a mechanical engineering undergrad. Then he did his Ph.D. at MIT with a focus on spectroscopy,” says Paidi. “His research topics were interesting and the problems he was exploring – things like breast cancer and glucose monitoring – were important and interesting. It was obvious that his lab would emerge as a catalyst in this fast-moving field. It inspired me to explore the areas at the intersection of engineering, biology and medicine.”
Barman encouraged Paidi to take up certain projects that were interesting or challenging. “That helped me map my own trajectory in life sciences,” Paidi says. “He is enthusiastic about students driving the projects and provides them the flexibility to choose the subjects they wish to pursue. In him I found a great mentor and scientist from whom I could learn.”
Paidi describes the SLAS Graduate Education Fellowship Grant as a great opportunity for people who want to apply engineering expertise to life sciences research. This year was the third time that Paidi applied for the grant, because he knew how valuable it would be for his work. He’s glad he kept pursuing it.
“It’s a two-year grant that offers researchers sufficient time to work on projects. Certain grants offer only a year of support. It’s challenging to complete a project in that timeframe. You need time to start the project, modify protocol if necessary, complete your work and then publish it. The SLAS grant allows you to do your research from start to finish.”
He adds that the Society’s support extends well beyond the monetary award. “The community and the annual SLAS International Conference and Exhibition open to you a network of people to meet and build relationships. That is one of the key differentiating aspects of this grant,” says Paidi.
The fellowship grant is not the first time Paidi has been recognized by SLAS. He also was a finalist for the 2017 SLAS Graduate Education Fellowship Grant, which enabled him to attend SLAS2018 via the SLAS Tony B. Academic Travel Award program.
At SLAS2018, he enjoyed the additional honor of sharing his work, “Label-Free Raman Spectroscopy for Rapid Identification of Biologics,” at the inaugural SLAS Ignite Academic Theater. His presentation sparked many conversations and opened opportunities for collaboration.
“SLAS Ignite was a great opportunity, especially because of the location within the exhibition. It drew a good audience that had a great mix of academic and industry people,” says Paidi. “After the presentation, the questions were insightful, and people wanted to meet to discuss the research. Some researchers contacted my advisor after the conference to discuss potential avenues for collaboration. Presenting your work at the SLAS conference is important. It gives you an opportunity to evaluate how best your academic projects can meet actual needs in health care or industry.”
Barman, describing the networking and interaction opportunities that SLAS offers as outstanding, also notes that earning a trip to the conference was particularly important for Paidi’s work to advance. “SLAS does a tremendous job in balancing academia and industry. That is a hard combination to get right,” says Barman. “Students get to know a lot more about what's being done in industry, cutting edge products coming out, certain aspects of interest to incorporate into their own research or something that they want to pursue in the future.”
Paidi amplified his time at SLAS2018 by pursuing a free one-on-one SLAS mentoring session. An industry professional carefully examined Paidi’s CV in advance of the conference and then at an appointment held during the event, talked with Paidi about his goals, offered constructive feedback and strategized Paidi’s search for a post-doctoral position.
“I want to support SLAS programs such as this in the future,” says Paidi, who would like to be more involved in the community by mentoring others, joining a planning committee or reviewing manuscripts for SLAS’s two PubMed:MEDLINE-indexed scientific journals, SLAS Discovery (Advancing Life Sciences R&D) and SLAS Technology (Translating Life Sciences Innovation). “There are so many opportunities within SLAS for students and early career professionals,” he says. “I’m ready to jump in wherever I can help.”
The application process for 2019 grant awards will begin in fall 2018. Visit SLAS Graduate Education Fellowship Grant Program for more information on that program.
Degree-seeking graduate students may also consider applying for the SLAS Visiting Graduate Researcher Grant Program, also opening in fall 2018. This program is aimed at North American or European students at their home institution who are invited to conduct short-term doctoral research or participate in a mentored or independent research project with a faculty member at a different host institution. The program offers a stipend to cover the graduate student’s expenses for a visiting research stay of four weeks to six months.